Of the seven human herpesviruses, varicella zoster virus (VZV) is still among the most important in terms of disease frequency and clinical problems. Primary infection with VZV results in chickenpox or varicella, usually unremarkable in normal children, but capable of developing serious consequences in leukemic children or young adults. Reactivation of VZV results in zoster or shingles. This is characterized by a painful vesicular eruption which resolves within a few weeks. However, as with chickenpox, complications can arise which include blindness, encephalitis, myelitis and post herpetic neuralgia. This last sequela of zoster can persist for years and is the cause of an increasing amount of suffering in the aging U.S. population. At present little concerning the molecular details of either varicella or zoster infection (including latency) are understood. Work from several laboratories has however shown that 1) promoter elements of VZV genes appear to be unique, 2) the properties of the gene regulatory proteins of VZV are often quite distinct from those of their herpes simplex virus (HSV) counterparts, and 3) during latency VZV expresses at least the mRNAs (and presumably the polypeptides) corresponding to several gene regulatory protteins that may make up the earliest events in the lytic cycle. We plan to examine these aspects of VZV infection via the following specific aims: 1) Fine mapping of two already identified VZV promoter elements, 2) Analysis of the mechanism of action of the VZV ORF29 protein in VZV gene regulation, 3) Analysis of the role of the ORF63 protein in VZV infection and 4) characterization of the interaction of a cellular protein with the VZV ORF62 protein.